Transient Receptor Potential Melastatin 2 Enhances Vascular Reactivity During Development of Atherosclerosis in Mice.

Background To investigate the function of transient receptor potential melastatin 2 (TRPM2) in vascular reactivity induced by 5-hydroxytryptamine (5-HT) in the aorta during development of atherosclerosis in mice. Methods Forty mice were randomly divided into 4 groups: C57BL/6J on normal diet (C57 + ND), C57BL/6J on high-fat diet (C57 + HFD), apolipoprotein E gene knockout mice (ApoE^−/−) on ND (ApoE^−/− + ND), and ApoE^−/− on HFD (ApoE^−/− + HFD). They were fed with a ND or HFD for 16 weeks. Aortic TRPM2 expression and isometric contractions were analyzed. Results In the ApoE^−/− + HFD group, body weight, blood glucose, and blood lipid concentrations were increased, and aortic plaques were developed. Compared with the other 3 groups, aortic TRPM2 mRNA and protein levels were significantly increased in the ApoE^−/− + HFD group (P < 0.01). Aortic reactivity to 5-HT was enhanced in ApoE^−/− + HFD mice with lower EC₅₀ values. The enhanced reactivity to 5-HT was significantly inhibited by TRPM2 inhibitors, N - p -amylcinnamoyl anthranilic acid (1 µmol/l) and 2-aminoethyl diphenylborinate (10 µmol/l). Conclusions Aortic TRPM2 expression is upregulated in ApoE knockout mice fed with a HFD. Upregulation of TRPM2 enhances 5-HT vascular reactivity during development of atherosclerosis. [ABSTRACT FROM AUTHOR]